US12497450B2ActiveUtilityA1

Claudin 6 antibodies and uses thereof

66
Assignee: INTEGRAL MOLECULAR INCPriority: Feb 15, 2019Filed: Jan 4, 2022Granted: Dec 16, 2025
Est. expiryFeb 15, 2039(~12.6 yrs left)· nominal 20-yr term from priority
Inventors:Ross Stewart ChambersJoseph RuckerThomas CharpentierLewis J. StaffordBrad ScrenciTrevor BarnesBenjamin Doranz
A61K 40/4202A61K 40/31A61K 40/11C07K 2317/92C07K 2317/31C07K 2317/565A61K 47/6849A61K 2039/5156A61K 39/395C07K 2317/34C07K 2317/33A61K 2039/505C07K 2317/622A61P 35/00C07K 2319/33C07K 2319/03C07K 2317/515C07K 2317/24C07K 2317/56C07K 16/28C07K 16/30
66
PatentIndex Score
0
Cited by
169
References
32
Claims

Abstract

Antibodies and compositions against Claudin 6 and uses thereof are provided.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A bi-specific antibody comprising a first antigen binding region that binds to Claudin 6 and a second antigen binding region that binds to a different antigen, wherein the first antigen binding region comprises:
 a heavy chain variable region comprising a heavy chain CDR1 (HCDR1), CDR2 (HCDR2), and CDR3 (HCDR3), and a light chain variable region comprising a light chain CDR1 (LCDR1), CDR2 (LCDR2), and CDR3 (LCDR3), and wherein the bispecific antibody has:   a HCDR1 of SEQ ID NO: 139, HCDR2 of SEQ ID NO: 140, and HCDR3 of SEQ ID NO: 82, a LCDR1 of SEQ ID NO: 83; a LCDR2 of SEQ ID NO: 84; and a LCDR3 of SEQ ID NO: 85;   a HCDR1 of SEQ ID NO: 141, HCDR2 of SEQ ID NO: 142, and HCDR3 of SEQ ID NO: 57, a LCDR1 of SEQ ID NO: 87; a LCDR2 of SEQ ID NO: 88; and a LCDR3 of SEQ ID NO: 89;   a HCDR1 of SEQ ID NO: 143, HCDR2 of SEQ ID NO: 144, and HCDR3 of SEQ ID NO: 92, a LCDR1 of SEQ ID NO: 93; a LCDR2 of SEQ ID NO: 88; and a LCDR3 of SEQ ID NO: 94;   a HCDR1 of SEQ ID NO: 145, HCDR2 of SEQ ID NO: 146, and HCDR3 of SEQ ID NO: 97, a LCDR1 of SEQ ID NO: 98; a LCDR2 of SEQ ID NO: 99; and a LCDR3 of SEQ ID NO: 100;   a HCDR1 of SEQ ID NO: 25, HCDR2 of SEQ ID NO: 26, and HCDR3 of SEQ ID NO: 27, a LCDR1 of SEQ ID NO: 22; a LCDR2 of SEQ ID NO: 23; and a LCDR3 of SEQ ID NO: 24;   a HCDR1 of SEQ ID NO: 31, HCDR2 of SEQ ID NO: 32, and HCDR3 of SEQ ID NO: 33, a LCDR1 of SEQ ID NO: 28; a LCDR2 of SEQ ID NO: 29; and a LCDR3 of SEQ ID NO: 30;   a HCDR1 of SEQ ID NO: 37, HCDR2 of SEQ ID NO: 38, and HCDR3 of SEQ ID NO: 39, a LCDR1 of SEQ ID NO: 34; a LCDR2 of SEQ ID NO: 29; and a LCDR3 of SEQ ID NO: 36;   a HCDR1 of SEQ ID NO: 43, HCDR2 of SEQ ID NO: 44, and HCDR3 of SEQ ID NO: 45, a LCDR1 of SEQ ID NO: 40; a LCDR2 of SEQ ID NO: 41; and a LCDR3 of SEQ ID NO: 43;   a HCDR1 of SEQ ID NO: 25, HCDR2 of SEQ ID NO: 26, and HCDR3 of SEQ ID NO: 27, a LCDR1 of SEQ ID NO: 22; a LCDR2 of SEQ ID NO: 23; and a LCDR3 of SEQ ID NO: 24;   a HCDR1 of SEQ ID NO: 31, HCDR2 of SEQ ID NO: 46, and HCDR3 of SEQ ID NO: 33, a LCDR1 of SEQ ID NO: 28; a LCDR2 of SEQ ID NO: 29; and a LCDR3 of SEQ ID NO: 30;   a HCDR1 of SEQ ID NO: 37, HCDR2 of SEQ ID NO: 48, and HCDR3 of SEQ ID NO: 39, a LCDR1 of SEQ ID NO: 47; a LCDR2 of SEQ ID NO: 29; and a LCDR3 of SEQ ID NO: 36;   a HCDR1 of SEQ ID NO: 43, HCDR2 of SEQ ID NO: 49, and HCDR3 of SEQ ID NO: 45, a LCDR1 of SEQ ID NO: 40; a LCDR2 of SEQ ID NO: 41; and a LCDR3 of SEQ ID NO: 42;   a HCDR1 of SEQ ID NO: 53, HCDR2 of SEQ ID NO: 54, and HCDR3 of SEQ ID NO: 33, a LCDR1 of SEQ ID NO: 50; a LCDR2 of SEQ ID NO: 51; and a LCDR3 of SEQ ID NO: 52;   a HCDR1 of SEQ ID NO: 55, HCDR2 of SEQ ID NO: 54, and HCDR3 of SEQ ID NO: 33, a LCDR1 of SEQ ID NO: 50; a LCDR2 of SEQ ID NO: 51; and a LCDR3 of SEQ ID NO: 52;   a HCDR1 of SEQ ID NO: 56, HCDR2 of SEQ ID NO: 101, and HCDR3 of SEQ ID NO: 57, a LCDR1 of SEQ ID NO: 58; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 60;   a HCDR1 of SEQ ID NO: 56, HCDR2 of SEQ ID NO: 101, and HCDR3 of SEQ ID NO: 61, a LCDR1 of SEQ ID NO: 58; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 60;   a HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO: 101, and HCDR3 of SEQ ID NO: 63, a LCDR1 of SEQ ID NO: 64; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 60;   a HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO: 101, and HCDR3 of SEQ ID NO: 65, a LCDR1 of SEQ ID NO: 64; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 60;   a HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO: 101, and HCDR3 of SEQ ID NO: 66, a LCDR1 of SEQ ID NO: 64; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 60;   a HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO: 101, and HCDR3 of SEQ ID NO: 67, a LCDR1 of SEQ ID NO: 64; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 60;   a HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO: 101, and HCDR3 of SEQ ID NO: 65, a LCDR1 of SEQ ID NO: 58; a LCDR2 of SEQ ID NO: 68; and a LCDR3 of SEQ ID NO: 60;   a HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO: 101, and HCDR3 of SEQ ID NO: 126, a LCDR1 of SEQ ID NO: 58; a LCDR2 of SEQ ID NO: 68; and a LCDR3 of SEQ ID NO: 60;   a HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO: 101, and HCDR3 of SEQ ID NO: 69, a LCDR1 of SEQ ID NO: 58; a LCDR2 of SEQ ID NO: 68; and a LCDR3 of SEQ ID NO: 60;   a HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO: 101, and HCDR3 of SEQ ID NO: 69, a LCDR1 of SEQ ID NO: 64; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 70;   a HCDR1 of SEQ ID NO: 71, HCDR2 of SEQ ID NO: 72, and HCDR3 of SEQ ID NO: 73, a LCDR1 of SEQ ID NO: 74; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 75;   a HCDR1 of SEQ ID NO: 76, HCDR2 of SEQ ID NO: 77, and HCDR3 of SEQ ID NO: 78, a LCDR1 of SEQ ID NO: 147; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 79;   a HCDR1 of SEQ ID NO: 80, HCDR2 of SEQ ID NO: 81, and HCDR3 of SEQ ID NO: 82, a LCDR1 of SEQ ID NO: 83; a LCDR2 of SEQ ID NO: 84; and a LCDR3 of SEQ ID NO: 85;   a HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO: 86, and HCDR3 of SEQ ID NO: 57, a LCDR1 of SEQ ID NO: 87; a LCDR2 of SEQ ID NO: 88; and a LCDR3 of SEQ ID NO: 89;   a HCDR1 of SEQ ID NO: 90, HCDR2 of SEQ ID NO: 91, and HCDR3 of SEQ ID NO: 92, a LCDR1 of SEQ ID NO: 93; a LCDR2 of SEQ ID NO: 88 and a LCDR3 of SEQ ID NO: 94;   a HCDR1 of SEQ ID NO: 95, HCDR2 of SEQ ID NO: 96, and HCDR3 of SEQ ID NO: 97, a LCDR1 of SEQ ID NO: 98; a LCDR2 of SEQ ID NO: 99; and a LCDR3 of SEQ ID NO: 100;   a HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO: 101, and HCDR3 of SEQ ID NO: 57, a LCDR1 of SEQ ID NO: 58; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 60; or   a HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 57, a LCDR1 of SEQ ID NO: 87; a LCDR2 of SEQ ID NO: 88; and a LCDR3 of SEQ ID NO: 89.   
     
     
         2 . The bi-specific antibody of  claim 1 , wherein the second antigen binding region binds to CD3. 
     
     
         3 . The bi-specific antibody of  claim 1 , wherein the antigen binding region that binds to Claudin 6 is in a scFv or Fab format. 
     
     
         4 . The bi-specific antibody of  claim 1 , wherein the second antigen binding region that binds to a different antigen is in a scFv or Fab format. 
     
     
         5 . The bi-specific antibody of  claim 1 , wherein the antigen binding region that binds to Claudin 6 is in a scFv format, and the second antigen binding region that binds to a different antigen is in a Fab format. 
     
     
         6 . The bi-specific antibody of  claim 1 , wherein the antigen binding region that binds to Claudin 6 is in a Fab format, and the second antigen binding region that binds to a different antigen is in a scFv format. 
     
     
         7 . The bi-specific antibody of  claim 2 , wherein the antigen binding region that binds to Claudin 6 is in a Fab format, and the second antigen binding region that binds CD3 is in a scFv format. 
     
     
         8 . The bi-specific antibody of  claim 2 , wherein the antigen binding region that binds to Claudin 6 is in a scFv format, and the second antigen binding region that binds CD3 is in a Fab format. 
     
     
         9 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises a HCDR1 of SEQ ID NO: 53, a HCDR2 of SEQ ID NO: 54, a HCDR3 of SEQ ID NO: 33, a LCDR1 of SEQ ID NO: 50; a LCDR2 of SEQ ID NO: 51; and a LCDR3 of SEQ ID NO: 52. 
     
     
         10 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises:
 a) a light chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 19, the light chain variable region comprising:
 i. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 50; 
 ii. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 51; 
 iii. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 52; and 
   b) a heavy chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 18, the heavy chain variable region comprising:
 i. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 53; 
 ii. a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 54; and, 
 iii. a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 33. 
   
     
     
         11 . The bi-specific antibody of  claim 10 , wherein the light chain variable region of the first antigen binding region has at least 95% identity to the amino acid sequence of SEQ ID NO: 19, and the heavy chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 18. 
     
     
         12 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises a light chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 19, the light chain variable region comprising: i. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 50; ii. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 51; and, iii. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 52. 
     
     
         13 . The bi-specific antibody of  claim 12 , wherein the light chain variable region of the first antigen binding region has at least 95% identity to the amino acid sequence of SEQ ID NO: 19. 
     
     
         14 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises a HCDR1 of SEQ ID NO: 62, a HCDR2 of SEQ ID NO: 125, a HCDR3 of SEQ ID NO: 69, a LCDR1 of SEQ ID NO: 58; a LCDR2 of SEQ ID NO: 68; and a LCDR3 of SEQ ID NO: 60. 
     
     
         15 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises a HCDR1 of SEQ ID NO: 62, a HCDR2 of SEQ ID NO: 125, a HCDR3 of SEQ ID NO: 67, a LCDR1 of SEQ ID NO: 64; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 60. 
     
     
         16 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises:
 a) a light chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 118, the light chain variable region comprising: i. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 58; ii. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 68; iii. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 60; and   b) a heavy chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 117, the heavy chain variable region comprising: i. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 62; ii. a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 125; and, iii. a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 69.   
     
     
         17 . The bi-specific antibody of  claim 16 , wherein the light chain variable region of the first antigen binding region has at least 95% identity to the amino acid sequence of SEQ ID NO: 118, and the heavy chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 117. 
     
     
         18 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises:
 a) a light chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 112, the light chain variable region comprising: i. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 64; ii. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 59; iii. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 60; and   b) a heavy chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 111, the heavy chain variable region comprising: i. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 62; ii. a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 125; and, iii. a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 67.   
     
     
         19 . The bi-specific antibody of  claim 18 , wherein the light chain variable region of the first antigen binding region has at least 95% identity to the amino acid sequence of SEQ ID NO: 112, and the heavy chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 111. 
     
     
         20 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises a HCDR1 of SEQ ID NO: 62, a HCDR2 of SEQ ID NO: 125, a HCDR3 of SEQ ID NO: 66, a LCDR1 of SEQ ID NO: 64; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 60. 
     
     
         21 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises:
 a) a light chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 110, the light chain variable region comprising: i. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 64; ii. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 59; iii. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 60; and   b) a heavy chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 109, the heavy chain variable region comprising: i. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 62; ii. a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 125; and, iii. a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 66.   
     
     
         22 . The bi-specific antibody of  claim 1 , wherein the light chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 110, and the heavy chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 109. 
     
     
         23 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises a light chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 110, the light chain variable region comprising: i. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 64; ii. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 59; and iii. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 60. 
     
     
         24 . The bi-specific antibody of  claim 23 , wherein the light chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 110. 
     
     
         25 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises a HCDR1 of SEQ ID NO: 62, a HCDR2 of SEQ ID NO: 125, a HCDR3 of SEQ ID NO: 65, a LCDR1 of SEQ ID NO: 64; a LCDR2 of SEQ ID NO: 59; and a LCDR3 of SEQ ID NO: 60. 
     
     
         26 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises:
 a) a light chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 108, the light chain variable region comprising: i. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 64; ii. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 59; iii. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 60; and   b) a heavy chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 107, the heavy chain variable region comprising: i. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 62; ii. a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 125; and iii. a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 65.   
     
     
         27 . The bi-specific antibody of  claim 26 , wherein the light chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 108, and the heavy chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 107. 
     
     
         28 . The bi-specific antibody of  claim 1 , wherein the first antigen binding region comprises a light chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 108, the light chain variable region comprising: i. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 64; ii. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 59; and, iii. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 60. 
     
     
         29 . The bi-specific antibody of  claim 28 , wherein the light chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 108. 
     
     
         30 . A nucleic acid molecule encoding a bispecific antibody of  claim 1 . 
     
     
         31 . A pharmaceutical composition comprising a bispecific antibody of  claim 1 , or a nucleic acid molecule encoding the same. 
     
     
         32 . A cell comprising the nucleic acid molecule of  claim 30 .

Cited by (0)

No later patents cite this yet.

References (0)

No backward citations on record.